benzofurans and Heart-Diseases

Both Yucheng and Yusho were events of accidental exposure to highly doses of polychlorinated biphenyls and dibenzofurans in Asian people. Mortality experiences caused by various diseases were reported in both cohorts with similar and dissimilar findings. We thus conducted a meta-analysis of two cohorts to reevaluate the effects of PCBs and PCDFs on major causes of mortalities. Two recently updated Yucheng and Yusho mortality studies were included. For selected diseases, standardized mortality ratios (SMR) and 95% confidence intervals (95% CI) were extracted. Meta-analyses were conducted using a random-effects model only when heterogeneity (I(2)  > 50% and/or p value <0.10 by the Q test) was not found. A total of 1,803 Yucheng subjects (male, N = 830; female, N = 973) with 48,751 person-years of follow-up and 1,664 Yusho subjects (male, N = 860; female, N = 804) with 50,773 person-years are included. An increase in all-cause mortality (pooled SMR=1.2, 95% CI: 1.1-1.3, I(2)  = 0.0%), all cancers (pooled SMR=1.3, 95% CI: 1.1-1.6, I(2)  = 0.0%), lung cancer (pooled SMR=1.7, 95% CI: 1.2-2.3, I(2) =0.0%), heart disease (pooled SMR=1.3, 95% CI: 1.0-1.7, I(2)  = 43.4%) and hepatic disease (pooled SMR=1.9, 95% CI: 1.3-2.8, I(2)  = 0.0%) were found in pooled males. Significant elevation from liver cancer was found in pooled females (pooled SMR=2.0, 95% CI: 1.1-3.6, I(2)  = 0.0%). This meta-analysis of Yucheng and Yusho cohorts showed similar elevation from all cancer, lung cancer, heart disease and hepatic disease mortalities in exposed men. Furthermore, a new finding of elevated liver cancer mortality in exposed women was identified.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzofurans; Child; Child, Preschool; Dibenzofurans, Polychlorinated; Environmental Exposure; Female; Food Contamination; Heart Diseases; Humans; Infant; Infant, Newborn; Liver Diseases; Male; Middle Aged; Neoplasms; Poisoning; Polychlorinated Biphenyls; Young Adult

Heart aging is characterized by structural and diastolic dysfunction of the heart. However, there is still no effective drug to prevent and treat the abnormal changes in cardiac function caused by aging. Here, we present the preventive effects of emodin and its derivative Kanglexin (KLX) against heart aging. We found that the diastolic dysfunction and cardiac remodeling in mice with D-galactose (D-gal)-induced aging were markedly mitigated by KLX and emodin. In addition, the senescence of neonatal mouse cardiomyocytes induced by D-gal was also reversed by KLX and emodin treatment. However, KLX exhibited better anti-heart aging effects than emodin at the same dose. Dysregulated mitophagy was observed in aging hearts and in senescent neonatal mouse cardiomyocytes, and KLX produced a greater increase in mitophagy than emodin. The mitophagy-promoting effects of KLX and emodin were ascribed to their abilities to enhance the protein stability of Parkin, a key modulator in mitophagy, with different potencies. Molecular docking and SPR analysis demonstrated that KLX has a higher affinity for the ubiquitin-like (UBL) domain of Parkin than emodin. The UBL domain might contribute to the stabilizing effects of KLX on Parkin. In conclusion, this study identifies KLX and emodin as effective anti-heart aging drugs that activate Parkin-mediated mitophagy and outlines their putative therapeutic importance.

Topics: Aging; Animals; Anthraquinones; Benzofurans; Disease Models, Animal; Emodin; Female; Galactose; Heart Diseases; Mice; Mitophagy; Molecular Docking Simulation; Myocytes, Cardiac; Quinolines; Random Allocation; Ubiquitin-Protein Ligases

Cardiovascular complications have been well documented as the downside to conventional cancer chemotherapy. As a notable side effect of cisplatin (CDDP), cardiotoxicity represents a major obstacle to the successful treatment of cancer. It has been reported that Salvianolic acid B (SalB) possesses cardioprotective quality. However, the effect of SalB on cardiac damage caused by conventional cancer chemotherapy remains unclear. In this study, we clarified the protective effect of SalB on cisplatin-induced heart injury. Furthermore, in H9c2 cells, SalB dramatically reduced cisplatin-induced apoptosis and oxidative stress by modulating the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway. In conclusion, SalB had great potential in mitigating cisplatin-induced cardiac injury. Furthermore, more attention should be placed on natural active compounds containing SalB with antioxidant effects for the treatment of cardiomyopathy.

Topics: Animals; Antineoplastic Agents; Antioxidants; Benzofurans; Cell Line; Cell Survival; Cisplatin; Creatine Kinase, MB Form; Heart; Heart Diseases; Heme Oxygenase-1; L-Lactate Dehydrogenase; Male; Mice, Inbred C57BL; Myocardium; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; Oxidative Stress; Rats; Signal Transduction; Stroke Volume

Cardiac dysfunction is the main cause of multi-organ failure following sepsis within critical care units. The present study aimed to investigate the effects of the small molecule inhibition of cyclic GMP-AMP synthase (cGAS), RU.521, on cardiac function in mice with sepsis.. Sepsis was induced in mice via intraperitoneal lipopolysaccharide (LPS) injection (10 mg/kg, i.p.). Mice subsequently received 5 mg/kg RU.521 within 10 min form LPS injection. The cardiac function, inflammatory factor and oxidative stress of mice were examined for 24 h following LPS injection.. RU.521 was indicated to significantly increase the cardiac function of mice with sepsis. In addition, the inflammatory responses, oxidative stress and apoptosis in hearts of sepsis mice were markedly mitigated by RU.521. Moreover, inhibition of Sirt3 inhibited the protective effects of RU.521 on mice with sepsis.. The current study indicated that RU.521 alleviated the inflammatory response and alleviated the damage induced by oxidative stress, leading to cardiac protection via increased Sirt3 expression in the hearts of mice with sepsis.

Topics: Animals; Apoptosis; Benzofurans; Heart Diseases; Lipopolysaccharides; Male; Mice; Nucleotidyltransferases; Oxidative Stress; Sepsis; Signal Transduction

Agents against atrial structural remodeling (ASR) are thought to block the occurrence of atrial fibrillation (AF). The aim of this study was to investigate the effects of DL-3-n-butylphthalide (NBP) on ASR and AF formation in rats with heart failure (HF) induced by myocardial infarction. The heart failure rats established 1 week after ligating left anterior descending coronary artery were randomly treated with vehicle (HF group, n = 24), or treated with DL-3-n-butylphthalide (100 mg/kg body weight) (NBP group, n = 26) for 4 weeks. Eighteen rats that underwent the same surgery but without ligating artery treated with vehicle were used as sham group (n = 18). Echocardiography, AF inducibility test, atrial fibrosis, gap junction, cytokine expression and serum antioxidant capacity analysis were detected at follow-up. Treatment of NBP for 4 weeks significantly improved cardiac function (P < 0.05), reduced AF inducibility and duration time (P < 0.05), and attenuated atrial fibrosis (P < 0.05). NBP also up-regulated protein expression of both overall Cx43 and phosphorylated Cx43 (P < 0.05) and improved the distribution of Cx43. Furthermore, NBP significantly inhibited the expression of TNF-α, NF-κB, and TGF-β1 and up-regulated Nrf2 and HO-1 protein expression with an increased serum T-AOC, CAT, and SOD activities and a reduced serum MDA. Collectively, NBP prevented ASR and AF in rats with HF by inhibiting atrial fibrosis, resynchronizing gap junction remodeling through inhibiting TNF-α/NF-κB/TGF-β1-related inflammatory reactions, and up-regulating Nrf2/HO-1-mediated antioxidant effects. Therefore, NBP may be a promising agent as upstream therapy for the prevention of AF.

Topics: Animals; Atrial Remodeling; Benzofurans; Cardiotonic Agents; Heart Atria; Heart Diseases; Heme Oxygenase (Decyclizing); Male; NF-E2-Related Factor 2; NF-kappa B; Rats, Sprague-Dawley; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

Doxorubicin (DOX)-induced cardiotoxicity is a clinically complex syndrome that leads to significant pain to cancer survivors. Endoplasmic reticulum (ER) stress has been suggested to be an important contributor to myocardium dysfunction during this phenomenon. Our previous study proved that Salvianolic acid B (Sal B) protected against doxorubicin induced cardiac dysfunction by inhibiting ER stress and cardiomyocyte apoptosis. However, the underlying molecular mechanism is not yet clearly. In this study, we investigated the protective effect and mechanisms of Sal B againest DOX-induced cardiac injury and ER stress in vivo and in vitro. After pretreatment with Sal B (0.25, 0.5, 1mg/kg i.v.) for 7 days, male SD rats were intraperitoneally injected with a single dose of DOX (3mg/kg) every 2 days for three injections. The cardioprotective effect of Sal B was observed 2 weeks after the first administration. Adult rat ventricular myocytes were isolated and treated with Sal B (20μg/ml) for 6h and then exposed in DOX (1μm) for 4h. The cardiomyocyte contractility and the level of intracellular Ca

Topics: Animals; Apoptosis; Benzofurans; Calcium Signaling; Cardiotoxicity; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Doxorubicin; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Heart Diseases; Male; Membrane Potential, Mitochondrial; Myocardial Contraction; Myocytes, Cardiac; Protective Agents; Rats, Sprague-Dawley; Time Factors; TRPC Cation Channels

(+)-Usnic acid (UA) has been known to be a strong uncoupler, and mitochondrial and endoplasmic reticulum (ER)-related stresses are suggested to be involved in the mechanism of hepatotoxicity. However, it has not been clarified whether UA causes toxicity in other mitochondria-rich organs such as the heart. We elucidated whether UA induces cardiotoxicity and its mechanism. UA was orally administered to rats for 14 days, and laboratory and histopathological examinations were performed in conjunction with toxicogenomic analysis. As a result, there was no alteration in blood chemistry, whereas cytoplasmic rarefaction of myocardium was observed microscopically. This finding corresponded to the swollen mitochondria observed ultrastructurally. Immunohistochemically, expression of prohibitin, indicating mitochondrial imbalance, increased in the sarcoplasmic area. Toxicogenomic analysis highlighted the upregulation of gene groups consisting of oxidative stress, ER stress, and amino acid limitation. Interestingly, the number of upregulated genes was larger in the amino acid limitation-related gene group than that in other groups, implying that amino acid limitation might be one of the sources of oxidative stress, not only mitochondria and ER-originated stresses. In conclusion, the heart was manifested to be one of the target organs of UA. Mitochondrial imbalance with complex stresses may be involved in the toxic mechanism.

Topics: Amino Acids; Animals; Anti-Infective Agents; Benzofurans; Endoplasmic Reticulum Stress; Female; Gene Expression; Heart Diseases; Microarray Analysis; Myocardium; Oxidative Stress; Rats; Rats, Inbred F344; RNA

Although doxorubicin is an effective antitumor agent, the serious cardiotoxicity mediated by the production of reactive oxygen species has remained a considerable clinical problem. In China, salvianolic acids has been widely used for cardioprotection. To test whether salvianolic acids holds the potential to be protective against cardiotoxicity of doxorubicin, we created an acute cardiac injury mice model. Therapeutic treatment with salvianolic acids (40 mg/kg for 3 connective days) significantly reduced doxorubicin-induced (15 mg/kg) toxicity, including elevation of body weight and heart weight/tibia length ratio, decrease of creatine kinase, improvement of electrocardiography and heart vacuolation. Furthermore, the antioxidative effects of salvianolic acids were verified by oxygen radicals absorbance capacities assay in vitro and malondialdehyde detection in vivo, suggesting one possible mechanism of salvianolic acids on cardioprotection through blocking oxidative stress.

Topics: Animals; Antibiotics, Antineoplastic; Benzofurans; Body Weight; Caffeic Acids; Cardiotonic Agents; Creatine Kinase; Doxorubicin; Electrocardiography; Heart Diseases; Lactates; Male; Malondialdehyde; Mice; Myocardium; Oxidative Stress; Reactive Oxygen Species; Tissue Fixation

Monensin, a well-known ionophore antibiotic, may cause severe damage in myocardial cells. We investigated whether IRFI 042, a new analogue of vitamin E, may block lipid peroxidation in myocardial cells and in turn protect against monensin toxicity. Monensin toxicity was induced by repeated daily administration of the ionophore antibiotic (150 mg/kg/day for 7 days). Sham animals received by oral gavages only a saline solution and were used as controls. All animals were randomized to receive concomitantly by oral gavages IRFI 042 (20 mg/kg) or its vehicle. The experiment lasted 8 days. Survival rate, heart lipid peroxidation, studied by means of thiobarbituric acid-reactive substances (TBARs) levels, cardiac expression of endothelial nitric oxide (e-NOS) and histological analysis of the heart were performed. Monensin administration caused a decrease in survival rate. Mortality appeared following the second monensin injection and at day 7 caused a survival rate of 20%. Thereafter, no further mortality was observed. IRFI 042 administration improved survival rate. Injection of the ionophore antibiotic resulted in a marked cardiac lipid peroxidation and in a significant reduction in cardiac e-NOS message and protein expression. IRFI 042 decreased heart TBARs levels (Monensin + vehicle = 6.5 +/- 0.8 nmol/mg; Monensin + IRFI 042 = 3.2 +/- 1.1 nmol/mg; P < 0.001) and increased e-NOS message and protein expression. Histological analysis showed that IRFI 042 improved myocardial cells damage and enhanced the depressed e-NOS expression in chick heart samples following monensin administration. Our data suggest that IRFI 042 is a promising drug to reduce monensin cardio-toxicity in chicks.

Topics: Animals; Benzofurans; Blotting, Western; Chickens; Coccidiostats; Heart; Heart Diseases; Immunohistochemistry; Lipid Peroxidation; Male; Monensin; Myocardium; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Reverse Transcriptase Polymerase Chain Reaction; RNA; Survival Analysis; Thiobarbituric Acid Reactive Substances

Topics: Amiodarone; Benzofurans; Heart Diseases; Humans

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Interactions; Heart Diseases; Heart Ventricles; Humans; Kinetics; Pulmonary Fibrosis

Amiodarone is a useful antiarrhythmic agent whose pharmacokinetics are incompletely characterised. In order to optimise efficacy of an antiarrhythmic drug, information regarding plasma concentrations achieved during use of the drug is necessary. We report plasma amiodarone and desethylamiodarone concentrations in eight patients following intravenous infusion at a rate of 175 mg h-1 for the first 2 h, followed by infusion at a rate of 50 mg h-1 for a further 46 h a regimen very similar to that recommended by the manufacturers. In at least three of eight patients plasma concentrations were below the suggested therapeutic range of 1.0-2.5 mg l-1 from 3 to 16 h after the infusion was started. Our data suggests that larger doses of intravenous amiodarone than those previously recommended may be necessary to obtain optimal benefit from the drug.

Topics: Aged; Amiodarone; Benzofurans; Female; Heart Diseases; Humans; Infusions, Parenteral; Kinetics; Male; Middle Aged

Topics: Amiodarone; Benzofurans; Heart Diseases; Humans

Four cases of amiodarone neuropathy are reported. Patients presented a sensorimotor neuropathy with distal predominance. Improvement occurred after drug discontinuation. Nerve conduction velocities were significantly decreased. Other secondary effects of amiodarone were noted in two cases. In one case serum levels of amiodarone and N-monodesethylamiodarone were evaluated during and after treatment. Pathological study of nerve with morphometric evaluation was performed. Axonal degeneration changes were predominant in 3 cases. Aspects of segmental demyelination and remyelination were noted in one case and related to secondary demyelination. Numerous lysosomal inclusions were present in Schwann cells, fibroblasts, capillary endothelial and perithelial cells and in perineural cells. Similar inclusions have been observed in other drug-induced lipidosis. The factors responsible for this neuropathy are unknown. In one case, amiodarone-induced hepatic failure might explain the persisting high serum levels of the drug.

Topics: Adult; Aged; Amiodarone; Axons; Benzofurans; Heart Diseases; Humans; Inclusion Bodies; Male; Microscopy, Electron; Middle Aged; Nerve Fibers, Myelinated; Neural Conduction; Peripheral Nervous System Diseases; Schwann Cells; Sensation; Sural Nerve

Topics: Aged; Amiodarone; Benzofurans; Cholesterol; Female; Heart Diseases; Humans; Hyperglycemia; Male; Middle Aged; Triglycerides

Amiodarone, an iodine-containing drug used frequently in the treatment of cardiac arrhythmias and angina pectoris, has many effects on thyroid hormone metabolism, including decreasing the production of triiodothyronine (T3) and decreasing the clearance of thyroxine and reverse T3. These effects result in elevated serum thyroxine and reverse T3 concentrations and decreased serum T3 concentrations. In addition, iodine-induced hyperthyroidism or hypothyroidism may occur in patients chronically treated with amiodarone. This study is a retrospective analysis of the incidence of thyroid dysfunction in Lucca and Pisa, West Tuscany, Italy, and in Worcester, Massachusetts. Hyperthyroidism was a more frequent (9.6%) complication of amiodarone therapy in West Tuscany, where iodine intake is moderately low; hypothyroidism was more frequent (22%) in Worcester, where iodine intake is sufficient. In patients receiving chronic amiodarone therapy, clinically suspected hyperthyroidism is best confirmed by showing elevations in serum T3 or free T3 concentrations; hypothyroidism is best diagnosed by showing an elevated serum thyrotrophin concentration. Thyroid function should be carefully monitored in patients receiving amiodarone chronically, especially if they have goiter or Hashimoto's thyroiditis.

Topics: Adult; Aged; Amiodarone; Benzofurans; Female; Goiter; Heart Diseases; Humans; Hyperthyroidism; Hypothyroidism; Iodine; Italy; Long-Term Care; Male; Massachusetts; Middle Aged; Retrospective Studies; Thyroglobulin; Thyroid Diseases; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Plasma concentrations of T4, FT4, T3, rT3 and TBG, as well as of TSH before and after stimulation with TRH were studied in 25 patients, who had been treated with amiodarone for up to nine years. At the beginning of therapy, all the parameters mentioned above were found to be in the normal range in all patients. After two months of therapy, T4 had increased from 100 nmol/l +/- 24 nmol/l to 155 nmol/l +/- 32 nmol/l (p less than 0.01), and FT4 from 22 pmol/l +/- 10.5 pmol/l to 32 pmol/l +/- 8 pmol/l (p less than 0.01). T3 had decreased to the lower normal range (n.s.). TBG showed no significant changes. The TRH-tests had been normal in the beginning, but they remained positive in only 20% of the cases. At the end of the study, rT3 exceeded the normal range in all 25 patients. Two patients developed definite hyperthyroidism with elevations of T3 up to 4.7 nmol/l and 7.5 nmol/l, respectively. In one of them, we decided to discontinue amiodarone. Testing of thyroid function under antithyroid drug therapy revealed a hyperfunctioning autonomous adenoma, which was successfully eliminated by radioactive iodine therapy. In the other patient, it was not possible to withdraw amiodarone, so we initiated long-term treatment with antithyroid drugs. Our data support the assumption that amiodarone causes an impairment of the peripheral conversion of T4 to T3. As a result, one finds elevated serum concentrations of T4, which, in combination with the mainly negative TRH-test, must not be interpreted as proof of a hyperthyroid metabolic state being present. Hyperthyroidism is confirmed only if serum concentrations of T3 are also elevated.

Topics: Adolescent; Adult; Aged; Amiodarone; Benzofurans; Female; Heart Diseases; Humans; Male; Middle Aged; Retrospective Studies; Thyroid Function Tests; Thyroid Hormones

Myocardial size and contractility were measured by gated radionuclide ventriculography in 70 patients before and a mean of 66 days after beginning amiodarone therapy. The mean dose of amiodarone at the time of the second study was 481 mg. The mean left ventricular (LV) ejection fraction (EF) increased slightly, from 40% to 43% (p = 0.001). The mean right ventricular EF remained unchanged (38% to 39%, difference not significant [NS]). The LV end-diastolic volume (count-based method) increased by 9% (p = 0.01), but no change could be demonstrated for end-systolic volume (4%, NS). The LV stroke volume increased 19% (p = 0.001), but cardiac output remained unchanged (5%, NS) because the heart rate decreased by 9 beats/min (p = 0.001). The right ventricular end-diastolic volume increased by 12% (p = 0.01) and end-systolic volume increased by 11% (p = 0.03). Stroke volume increased by 18% (p = 0.005). There was no significant correlation between the change in LVEF and the pre-amiodarone LVEF, the time interval between studies, or with indexes of amiodarone effect (change in heart rate, QRS, QTc, TSH, amiodarone dosage). In 5 patients (7%), LVEF decreased significantly, requiring discontinuation of amiodarone therapy in 1 patient. At the time of the second study congestive heart failure was manifest in 19%, and there was a trend suggesting that congestive heart failure was more likely if the initial LVEF was less than or equal to 35% (p = 0.10). Thus, amiodarone may rarely adversely affect contractility, although myocardial contractility is typically unchanged. There is an associated small increase in the size of both ventricles.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiac Output; Female; Heart; Heart Diseases; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction; Radionuclide Imaging; Stroke Volume

The increasing use of amiodarone as antiarrhythmic drug has raised the possibilities of dangerous effects from amiodarone-digitalis interaction. We have studied twelve patients who were taking digitalis and to whom amiodarone was administered because of arrhythmias. We found a 75,42% increase of digitalis plasma levels (p less than 0,001) in the early days of amiodarone therapy, and a 52,1% increase (p less than 0,001) in the medium term. An inverse correlation was found (r = -0,65; p less than 0,05) between the plasma levels of digitalis during the steady-state control period and during the following 2-to-6 months evaluation. Acute episodes of cardiac failure caused in our patients an abrupt increase of digitalis plasma levels: in three patients digitalis toxicity occurred. Based on our experience, we recommend that the dose of digitalis be halved when the two drugs are given together in patients with various degree of cardiac failure; moreover digitalis plasma levels should be frequently monitored in these patients. On the other hand digitalis administered according to age, sex, weight, kidney function, together with amiodarone, can be given at full dosage in patients without cardiac failure.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digitalis Glycosides; Digoxin; Drug Interactions; Female; Heart Diseases; Humans; Male; Medigoxin; Middle Aged

The addition of amiodarone to digoxin therapy in nine children caused a sharp increase in digoxin serum concentrations (68% to 800%) in the presence of preserved serum creatinine and BUN concentrations. Digoxin half-life was prolonged. Digoxin accumulation could be attributed in part to the decrease in the renal clearance of digoxin resulting from inhibited tubular secretion of the drug and to the reduction in the distribution volume of digoxin caused by amiodarone. Creatinine clearance was not affected by amiodarone. This interaction appears to be more acute in children than in adults, presumably because of the more important role of the renal tubular secretion of digoxin in children. Whenever digoxin and amiodarone therapy are combined, the digoxin serum concentration should be monitored carefully, with appropriate reduction of the digoxin dose.

Topics: Adolescent; Amiodarone; Benzofurans; Cardiomyopathy, Dilated; Child; Child, Preschool; Creatinine; Digoxin; Drug Interactions; Heart Defects, Congenital; Heart Diseases; Humans; Infant; Male; Prospective Studies

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Evaluation; Female; Heart Diseases; Humans; Male; Middle Aged; Postoperative Complications

The effects of Amiodarone (1000-1400 mg/week, for a period ranging from 3 to 24 months) on thyroid gland function were studied in 45 patients with heart disease, using a new method of free thyroid hormone assay. Forty-four untreated patients and 11 normal subjects were used as controls. In treated patients the prevalence of dysthyroidism was 22,2% (15,6% hypothyroidism and 6,6% hyperthyroidism); the onset of dysthyroidism ranged from 20 days to 2 years after the beginning of treatment. In control patients the prevalence of dysthyroidism was 4,4% (2,2% hypothyroidism and 2,2% hyperthyroidism). In patients with hypothyroidism (TSH greater than 7 microunits/ml) T4 levels were generally low, while T3, fT4 and fT3 levels were normal. In treated patients with hyperthyroidism (fT3 greater than 5,3 pg/ml and fT4 greater than 16 pg/ml) T4 values were high, while T3 concentrations were in the normal range. In Amiodarone-treated euthyroid patients, mean T4, fT4 and rT3 values were significantly (p less than 0,01) higher than those of control subjects; TSH levels were normal in all the groups studied. These data suggest that Amiodarone can exert both a direct effect on the thyroid gland and the peripheral metabolism of thyroid hormones. The action on the thyroid gland is suggested by the high prevalence of dysthyroidism in Amiodarone-treated patients and by the high levels of T4 and fT4 observed in patients who did not show dysthyroidism. The action on the peripheral hormonal metabolism seems to be proved by the high levels of rT3 and by the prolongation of QTc interval.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Benzofurans; Female; Heart Diseases; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Thyroid Function Tests; Thyroid Gland

Topics: Adult; Amiodarone; Benzofurans; Female; Graves Disease; Heart Diseases; Humans

With ever increasing frequency potentially dangerous interactions are reported between Cardiac Glycosides and other drugs, particularly the antiarrhythmic one. The AA, carried out this work with the intent of studying the possible modifications produced by Q and A on the SDL. First of all the AA. retrospectively studied the SDL of patients treated with the associations Q-D and A-D and this SDL was compared with the SDL of patients treated with D alone. Then 10 subjects treated sequentially, at first with D alone and after with the Q-D (5 p.) and A-D (5 p.) association, were studied. The results obtained confirm the data of other AA. regarding the Q-D interaction; in fact, in the presence of this antiarrhythmic drug, the SDL increase significantly following the concomitant pharmacological effects of the Cardiac Glycosides. The SDL on the contrary seem not be influenced by the A-D association. The AA. then reviewed the literature about the mechanism of the Q-D interaction. The majority of the AA. agree outlining a reduction of the Volume of Distribution and of D Clearance, in consequence of the concomitant administration of Q, which would explain the high SDL obtained. In conclusion the AA. suggest, when the Q-D association is mandatory, a 50% reduction of the D maintenance dose and to check periodically the ECG and SDL.

Topics: Adult; Aged; Amiodarone; Benzofurans; Coronary Disease; Digoxin; Drug Interactions; Female; Heart Diseases; Humans; Hypertension; Male; Middle Aged; Quinidine; Rheumatic Heart Disease

Topics: Adrenergic beta-Antagonists; Adult; Amiodarone; Benzofurans; Heart Diseases; Humans; Male; Middle Aged; Verapamil

Topics: Adolescent; Adult; Aged; Amiodarone; Benzofurans; Blinking; Corneal Diseases; Female; Heart Diseases; Humans; Male; Middle Aged; Tears

6 cardiac patients were found to present various degrees of corneal involvement following systemic treatment with amiodarone. The clinical pattern of the keratopathy, its benign course and the pathophysiology are discussed. Lacrimal insufficiency or incomplete blinking seem to contribute to the severity of the keratopathy.

Topics: Adolescent; Adult; Aged; Amiodarone; Benzofurans; Corneal Diseases; Female; Heart Diseases; Humans; Male; Middle Aged

Amiodarone induces in patients "low T3-syndrome" characterized by normal T4. T3 resin uptake and free T3, contrasting with low T3 and free T4 values, and enhanced concentration of r-T3.

Topics: Amiodarone; Benzofurans; Heart Diseases; Humans; Syndrome; Triiodothyronine

Topics: Action Potentials; Adult; Aged; Amiodarone; Benzofurans; Carotid Arteries; Electrocardiography; Female; Heart; Heart Diseases; Humans; Male; Middle Aged; Time Factors

Topics: Antihypertensive Agents; Benzofurans; Cornea; Diuretics; Drug Hypersensitivity; Electrocardiography; Eye Diseases; Heart; Heart Diseases; Humans; Iatrogenic Disease; Lupus Erythematosus, Systemic; Quinidine

Topics: Adolescent; Adult; Aged; Benzoates; Benzofurans; Coronary Disease; Coumarins; Dipyridamole; Female; Gallic Acid; Glycolates; Heart Diseases; Humans; Hypotension; Lung Diseases; Male; Middle Aged; Myocardial Infarction; Myocardium; Oxygen Consumption; Propylamines; Vasodilator Agents; Verapamil; Xanthines

Topics: Adult; Aged; Benzofurans; Bronchitis; Bronchodilator Agents; Ephedrine; Female; Heart Diseases; Humans; Lung Diseases; Male; Middle Aged; Phenothiazines; Pyrans; Theophylline; Tranquilizing Agents

Topics: Benzofurans; Cardiomyopathies; Disease; Electrocardiography; Furans; Heart Diseases; Hypoxia; Myocardium; Vasodilator Agents